“Overworking to death” is a phenomenon that has been noticeable in developing countries. The cause of death is mainly through ischemic strokes. While the victims’ occupations differed, they all shared a common characteristic, being positioned in a sedentary work, ranging from IT workers to doctors. This project’s aim was to develop a product that prevented or decreased the strokes that derived from sedentary overwork. This was mainly tackled by preventing one of the three causes of developing blood props, slowed blood flow. In order to gather rich data of the phenomenon, a qualitative study was conducted in China, during two months. By doing an extensive structured sampling, information rich data could be gathered during a short period of time. Data were derived from observations, questionnaires and an interview, which then was interpreted to customer needs and the final product specification. The final product became a trouser with an in built dynamic compression mechanic, that can compress the veins mostly during sitting activities, in order to prevent blood stasis. The compression mechanic works like the Chinese finger trap; compressing the calves while sitting and stretching the legs forward. It is made only out of polysaccharides fibres; cotton and corn.

We present a method for producing a cell-scaffold hybrid construct at the bedside. The construct is composed of plastic-compressed collagen together with a poly(e-caprolactone) (PCL)-knitted mesh that yields an integrated, natural-synthetic scaffold. This construct was evaluated by seeding of minced bladder mucosa, followed by proliferation in vitro. High mechanical strength in combination with a biological environment suitable for tissue growth was achieved through the creation of a hybrid construct that showed an increased tensile strength (17.9 +/- 2.6 MPa) when compared to plastic-compressed collagen (0.6 +/- 0.12 MPa). Intimate contact between the collagen and the PCL fabric was required to ensure integrity without delamination of the construct. This contact was achieved by surface alkaline hydrolysis of the PCL, followed by adsorption of poly(vinyl) alcohol. The improvement in hydrophilicity of the PCL-knitted mesh was confirmed through water contact angle measurements, and penetration of the collagen into the mesh was evaluated by scanning electron microscopy (SEM). Particles of minced bladder mucosa tissue were seeded onto this scaffold, and the proliferation was followed for 6 weeks in vitro. Results obtained from phase contrast microscopy, SEM, and histological staining indicated that cells migrated from the minced tissue particles and reorganized on the scaffold. Cells were viable and proliferative, with morphological features characteristic of urothelial cells. Proliferation reached the point at which a multilayer with a resemblance to stratified urothelium was achieved. This successful method could potentially be used for in vivo applications in reconstructive urology as an engineered autologous tissue transplant without the requirement for in vitro culture before transplantation.

Calcium phosphate cements (CPCs) are used as bone void fillers and as complements to hardware in fracture fixation. The aim of this thesis was to investigate the possibilities and limitations of the CPCs’ mechanical properties, and find out if these ceramic bone cements can carry application-specific loads, alone or as part of a construct. Recently developed experimental brushite and apatite cements were found to have a significantly higher strength in compression, tension and flexion compared to the commercially available CPCs chronOS™ Inject and Norian® SRS®. By using a high-resolution measurement technique the elastic moduli of the CPCs were determined and found to be at least twice as high compared to earlier measurements, and closer to cortical bone than trabecular bone. Using the same method, Poisson's ratio for pure CPCs was determined for the first time. A non-destructive porosity measurement method for wet brushite cements was developed, and subsequently used to study the porosity increase during in vitro degradation. The compressive strength of the experimental brushite cement was still higher than that of trabecular bone after 25 weeks of degradation, showing that the cement can carry high loads over a time span sufficiently long for a fracture to heal. This thesis also presents the first ever fatigue results for acidic CPCs, and confirms the importance of testing the materials under cyclic loading as the cements may fail at stress levels much lower than the material’s quasi-static compressive strength. A decrease in fatigue life was found for brushite cements containing higher amounts of monetite. Increasing porosity and testing in a physiological buffer solution (PBS), rather than air, also decreased the fatigue life. However, the experimental brushite cement had a high probability of surviving loads found in the spine when tested in PBS, which has previously never been accomplished for acidic CPCs. In conclusion, available brushite cements may be able to carry the load alone in scenarios where the cortical shell is intact, the loading is mainly compressive, and the expected maximum stress is below 10 MPa. Under such circumstances this CPC may be the preferred choice over less biocompatible and non-degradable materials.

Calcium phosphate cements (CPCs) should ideally have mechanical properties similar to those of the bone tissue the material is used to replace or repair. Usually, the compressive strength of the CPCs is reported and, more rarely, the elastic modulus. Conversely, scarce or no data are available on Poisson's ratio and strain-to-crack-initiation. This is unfortunate, as data on the elastic response is key to, e.g., numerical model accuracy. In this study, the compressive behaviour of brushite, monetite and apatite cements was fully characterised. Measurement of the surface strains was done using a digital image correlation (DIC) technique, and compared to results obtained with the commonly used built-in displacement measurement of the materials testers. The collected data showed that the use of fixed compression platens, as opposed to spherically seated ones, may in some cases underestimate the compressive strength by up to 40%. Also, the built-in measurements may underestimate the elastic modulus by up to 62% as compared to DIC measurements. Using DIC, the brushite cement was found to be much stiffer (24.3 ± 2.3 GPa) than the apatite (13.5 ± 1.6 GPa) and monetite (7.1 ± 1.0 GPa) cements, and elastic moduli were inversely related to the porosity of the materials. Poisson's ratio was determined to be 0.26 ± 0.02 for brushite, 0.21 ± 0.02 for apatite and 0.20 ± 0.03 for monetite. All investigated CPCs showed low strain-to-crack-initiation (0.17–0.19%). In summary, the elastic modulus of CPCs is substantially higher than previously reported and it is concluded that an accurate procedure is a prerequisite in order to properly compare the mechanical properties of different CPC formulations. It is recommended to use spherically seated platens and measuring the strain at a relevant resolution and on the specimen surface.

Calcium phosphate cements (CPCs) are clinically used as injectable materials to fill bone voids and to improve hardware fixation in fracture surgery. In vivo they are dynamically loaded; nonetheless little is known about their fatigue properties. The aim of this study was to, for the first time, investigate the fatigue performance of a high strength, degradable (brushitic) CPC, and also evaluate the effect of cement porosity (by varying the liquid to powder ratio, L/P) and the environment (air at room temperature or in a phosphate buffered saline solution, PBS, at 37 degrees C) on the fatigue life. At a maximum compressive stress level of 15 MPa, the cements prepared with an L/P-ratio of 0.22 and 0.28 ml/g, corresponding to porosities of approximately 12% and 20%, had a 100% probability of survival until run-out of 5 million cycles, in air. When the maximum stress level, or the L/P-ratio, was increased, the probability of survival decreased. Testing in PBS at 37 degrees C led to more rapid failure of the specimens. However, the high-strength cement had a 100% probability of survival up to approximately 2.5 million cycles at a maximum compressive stress level of 10 MPa in PBS, which is substantially higher than some in vivo stress levels, e.g., those found in the spine. At 5 MPa in PBS, all specimens survived to run-out. The results found herein are important if clinical use of the material is to increase, as characterisation of the fatigue performance of CPCs is largely lacking from the literature.

The porosity of a calcium phosphate cement is a key parameter as it affects several important properties of the cement. However, a successful, non-destructive porosity measurement method that does not include drying has not yet been reported for calcium phosphate cements. The aim of this study was to evaluate isopropanol solvent exchange as such a method. Two different types of calcium phosphate cements were used, one basic (hydroxyapatite) and one acidic (brushite). The cements were allowed to set in an aqueous environment and then immersed in isopropanol and stored under three different conditions: at room temperature, at room temperature under vacuum (300 mbar) or at 37􏰀C. The specimen mass was monitored regularly. Solvent exchange took much longer time to reach steady state in hydroxyapatite cements compared to brushite cements, 350 and 18 h, respectively. Furthermore, the immersion affected the quasi-static compressive strength of the hydroxyapatite cements. However, the strength and phase composition of the brushite cements were not affected by isopropanol immersion, suggesting that isopropanol solvent exchange can be used for brushite calcium phosphate cements. The main advantages with this method are that it is non-destructive, fast, easy and the porosity can be evaluated while the cements remain wet, allowing for further analysis on the same specimen.

Bone loss and fractures may call for the use of bone substituting materials, such as calcium phosphate cements (CPCs). CPCs can be degradable, and, to determine their limitations in terms of applications, their mechanical as well as chemical properties need to be evaluated over longer periods of time, under physiological conditions. However, there is lack of data on how the in vitro degradation affects high-strength brushite CPCs over longer periods of time, that is, longer than it takes for a bone fracture to heal. This study aimed at evaluating the long-term in vitro degradation properties of a high-strength brushite CPC in three different solutions: water, phosphate buffered saline, and a serum solution. Microcomputed tomography was used to evaluate the degradation nondestructively, complemented with gravimetric analysis. The compressive strength, chemical composition, and microstructure were also evaluated. Major changes from 10 weeks onwards were seen, in terms of formation of a porous outer layer of octacalcium phosphate on the specimens with a concomitant change in phase composition, increased porosity, decrease in object volume, and mechanical properties. This study illustrates the importance of long-term evaluation of similar cement compositions to be able to predict the material’s physical changes over a relevant time frame.

Calcium phosphate cements (CPCs) are synthetic bone grafting materials that can be used in fracture stabilization and to fill bone voids after, e.g., bone tumour excision. Currently there are several calcium phosphate-based formulations available, but their use is partly limited by a lack of knowledge of their mechanical properties, in particular their resistance to mechanical loading over longer periods of time. Furthermore, depending on, e.g., setting conditions, the end product of acidic CPCs may be mainly brushite or monetite, which have been found to behave differently under quasi-static loading. The objectives of this study were to evaluate the compressive fatigue properties of acidic CPCs, as well as the effect of phase composition on these properties. Hence, brushite cements stored for different lengths of time and with different amounts of monetite were investigated under quasi-static and dynamic compression. Both storage and brushite-to-monetite phase transformation was found to have a pronounced effect both on quasi-static compressive strength and fatigue performance of the cements, whereby a substantial phase transformation gave rise to a lower mechanical resistance. The brushite cements investigated in this study had the potential to survive 5 million cycles at a maximum compressive stress of 13 MPa. Given the limited amount of published data on fatigue properties of CPCs, this study provides an important insight into the compressive fatigue behaviour of such materials.

The development of long-lasting zirconia-based ceramics for implants, which are not prone to hydrothermal aging, is not satisfactorily solved. Therefore, this study is conceived as an overall evaluation screening of novel ceria-stabilized zirconia-alumina-aluminate composite ceramics (ZA8Sr8-Ce11) with different surface topographies for use in clinical applications. Ceria-stabilized zirconia is chosen as the matrix for the composite material, due to its lower susceptibility to aging than yttria-stabilized zirconia (3Y-TZP). This assessment is carried out on three preclinical investigation levels, indicating an overall biocompatibility of ceria-stabilized zirconia-based ceramics, both in vitro and in vivo. Long-term attachment and mineralized extracellular matrix (ECM) deposition of primary osteoblasts are the most distinct on porous ZA8Sr8-Ce11p surfaces, while ECM attachment on 3Y-TZP and ZA8Sr8-Ce11 with compact surface texture is poor. In this regard, the animal study confirms the porous ZA8Sr8-Ce11p to be the most favorable material, showing the highest bone-to-implant contact values and implant stability post implantation in comparison with control groups. Moreover, the microbiological evaluation reveals no favoritism of biofilm formation on the porous ZA8Sr8-Ce11p when compared to a smooth control surface. Hence, together with the in vitro in vivo assessment analogy, the promising clinical potential of this novel ZA8Sr8-Ce11 as an implant material is demonstrated.

Arrowroot (Maranta arundinacea) is an edible starch, commercially available as powder, prepared from the roots of the plant family Marantaceae. Arrowroot is well known for its medicinal effects and use as chief ingredient in infant cookies. Arrowroot in film form is prepared and its microwave absorption characteristics, permittivity, loss factor, conductivity, skin depth, and heating coefficient are analyzed. The results are quite promising and can be concluded that arrowroot in film form is a potential candidate for several applications in medical field, when compared with well studied chitosan film

Beta tricalcium phosphate (b-TCP) bioceramics and chitosan biopolymers are used as biomedical implants because of their better biocompatibility and good bioresorption characteristics. As they are biomaterials, they have good interactions with microwave frequencies. b-TCP and chitosan powder, films, pellets, and gel are prepared and studied at the S-band microwave frequencies. Dielectric parameters such as dielectric constant, dielectric loss, conductivity, and S-parameters are evaluated. Dielectric parameters of different forms of b-TCP and chitosan show resemblance with that of human tissues. Hence, these materials can also be considered as potential phantoms for specific absorption rate measurements as well as in microwave imaging applications. V

Hydroxyapatite (HAp, Ca10(PO4)6(OH)2) bioceramic and chitosan (poly [(β-1-4) d-glucosamine]) biopolymer show good biocompatibility in vivo. They have biological origin and show excellent interactions with microwave. Microwave study of HAp made using different drying techniques and their composites with chitosan in the ISM band is presented. Pastes are made using HAp and chitosan with different ratios of mixing. The dielectric properties of this composites match with that of human fat, collagen tissues. Some of the compositions exhibit dielectric property close to that of natural bone. This makes them more biocompatible and better substitutes for natural bone. Thus composite bioceramics can be considered as phantom model constituents for imaging purposes.

Some biomaterials are osteoinductive, that is, they are able to trigger the osteogenic process by inducing the differentiation of mesenchymal stem cells to the osteogenic lineage. Although the underlying mechanism is still unclear, microporosity and specific surface area (SSA) have been identified as critical factors in material-associated osteoinduction. However, only sintered ceramics, which have a limited range of porosities and SSA, have been analyzed so far. In this work, we were able to extend these ranges to the nanoscale, through the foaming and 3D-printing of biomimetic calcium phosphates, thereby obtaining scaffolds with controlled micro- and nanoporosity and with tailored macropore architectures. Calcium-deficient hydroxyapatite (CDHA) scaffolds were evaluated after 6 and 12 weeks in an ectopic-implantation canine model and compared with two sintered ceramics, biphasic calcium phosphate and β-tricalcium phosphate. Only foams with spherical, concave macropores and not 3Dprinted scaffolds with convex, prismatic macropores induced significant ectopic bone formation. Among them, biomimetic nanostructured CDHA produced the highest incidence of ectopic bone and accelerated bone formation when compared with conventional microstructured sintered calcium phosphates with the same macropore architecture. Moreover, they exhibited different bone formation patterns; in CDHA foams, the new ectopic bone progressively replaced the scaffold, whereas in sintered biphasic calcium phosphate scaffolds, bone was deposited on the surface of the material, progressively filling the pore space. In conclusion, this study demonstrates that the high reactivity of nanostructured biomimetic CDHA combined with a spherical, concave macroporosity allows the pushing of the osteoinduction potential beyond the limits of microstructured calcium phosphate ceramics.

There is an urgent need of synthetic bone grafts with enhanced osteogenic capacity. This can be achieved by combining biomaterials with exogenous growth factors, which however can have numerous undesired side effects, but also by tuning the intrinsic biomaterial properties. In a previous study, we showed the synergistic effect of nanostructure and pore architecture of biomimetic calcium deficient hydroxyapatite (CDHA) scaffolds in enhancing osteoinduction, i.e. fostering the differentiation of mesenchymal stem cells to bone forming cells. This was demonstrated by assessing bone formation after implanting the scaffolds intramuscularly. The present study goes one step forward, since it analyzes the effect of the geometrical features of the same CDHA scaffolds, obtained either by 3D-printing or by foaming, on the osteogenic potential and resorption behaviour in a bony environment. After 6 and 12 weeks of intraosseous implantation, both bone formation and material degradation had been drastically affected by the macropore architecture of the scaffolds. Whereas nanostructured CDHA was shown to be highly osteoconductive both in the robocast and foamed scaffolds, a superior osteogenic capacity was observed in the foamed scaffolds, which was associated with their higher intrinsic osteoinductive potential. Moreover, they showed a significantly higher cell-mediated degradation than the robocast constructs, with a simultaneous and progressive replacement of the scaffold by new bone. In conclusion, these results demonstrate that the control of macropore architecture is a crucial parameter in the design of synthetic bone grafts, which allows fostering both material degradation and new bone formation. Statement of Significance 3D-printing technologies open new perspectives for the design of patient-specific bone grafts, since they allow customizing the external shape together with the internal architecture of implants. In this respect, it is important to design the appropriate pore geometry to maximize the bone healing capacity of these implants. The present study analyses the effect of pore architecture of nanostructured hydroxyapatite scaffolds, obtained either by 3D-printing or foaming, on the osteogenic potential and scaffold resorption in an in vivo model. While nanostructured hydroxyapatite showed excellent osteoconductive properties irrespective of pore geometry, we demonstrated that the spherical, concave macropores of foamed scaffolds significantly promoted both material resorption and bone regeneration compared to the 3D-printed scaffolds with orthogonal-patterned struts and therefore prismatic, convex macropores.

Calcium phosphate spheres are interesting alternatives for dental applications due to their chemical similarity to teeth and biocompatibility. A spherical shape with a hollow cores allows for loading of therapeutic agents for drug delivery which potentially could be combined with other applications such as tooth remineralization and treatment of hypersensitivity.

Precipitation reactions are one of the techniques used for synthesizing spherical particles, but little is known about the mechanism behind the sphere formation, which makes tuning of the material properties challenging. Previously, it has been shown that substituting ions can influence the crystallization process, which can enable greater control during the synthesis.In this study, several different substituting ions has been used in the synthesis of alkaline earth phosphates, to further investigate their role in sphere formation and to develop a robust synthesis technique.

Particles of alkaline earth phosphates (Ca, Sr and Ba) were synthesized with a precipitation reaction. Solutions with constituent anions and cations were mixed at room temperature, and substituting ions (Mg, Ca or Sr) were added before heating at 60-100 °C. Reaction times varied between 10 minutes to 24 hours. Characterization of precipitates was performed with SEM, DLS and FIB to analyze morphology, size and cross-sections of the spheres. Crystal structure and atomic composition was analyzed with XRD and ICP-OES.

Without substituting ions, precipitates had no specific shape and crystallized in an apatitic structure or as a hydrogenated phosphate. Substituting ions stabilized the initial amorphous phase during the reaction, hindering rapid crystal growth which allowed for self-assembly into hollow, spherical particles with a diameter between 300-700 nm. The phase composition and degree of ion substitution in the precipitates depended on the size and concentration of the substituting ions. The amount of substitution was determined in the range between 5-30 %, where precipitates with a low degree of substitution crystallized in a structure similar to β-tricalcium phosphate, whereas materials with a higher degree of substitution had an amorphous structure.

In this study it was shown that it was possible to obtain hollow, spherical particles of calcium-, strontium- and barium phosphate, by using substituting ions during a precipitation reaction. This indicates that the approach can be used to tailor the properties of spherical particles intended for dental applications.

Opioid therapy for chronic pain generally use controlled release formulations to deliver analgesic drugs around-the-clock. Controlled release dosage forms can enlarge the therapeutic effect by controlling the rate and site of release. However, with high drug content, opioid formulations are easily targeted for non-medical use. With the increasing concern of opioid abuse, tamper-resistance becomes an important attribute for opioid controlled-release dosage forms. Geopolymers have been studied as drug carrier for opioids to improve the tamper-resistance but there are still some issues, such as curing condition and fast drug release in acid, have not been studied in detail yet. This thesis focuses on the optimization and evaluation of the geopolymer-based formulation on its controlled-release and tamper-resistance properties with the aim of achieving optimal therapeutic outcomes and reducing abuse potential.

In this work, we showed some further improvement and evaluations on geopolymer-based drug formulations. The mechanical strength and porosity of geopolymers could be influenced by the curing conditions: high humidity for at least 48 hours could improve its mechanical strength, but elevated temperature only accelerated the geopolymerization but promoted water evaporation, leading to shrinkage and crack formation. Incorporating pH-sensitive organic polymers could improve the acid resistance of geopolymer formulation and thus reduce the risk of dose dumping. Comparing to a commercial opioid tablet, the geopolymer matrix have higher mechanical strength and could offer better resistance against physical manipulation and extraction under heating. The results provided solid experimental support on the potential for geopolymer as matrix for oral opioid delivery systems.

Tamper-resistance is an important property of controlled-release formulations of opioid drugs. Tamper-resistant formulations aim to increase the degree of effort required to override the controlled release of the drug molecules from extended-release formulations for the purpose of non-medical use. In this study, the resistance of a geopolymer-based formulation to tampering was evaluated by comparing it with a commercial controlled-release tablet using several methods commonly used by drug abusers. Because of its high compressive strength and resistance to heat, much more effort and time was required to extract the drug from the geopolymer-based formulation. Moreover, in the drug-release test, the geopolymer-based formulation maintained its controlled-release characteristics after milling, while the drug was released immediately from the milled commercial tablets, potentially resulting in dose dumping. Although the tampering methods used in this study does not cover all methods that abuser could access, the results obtained by the described methods showed that the geopolymer matrix increased the degree of effort required to override the controlled release of the drug, suggesting that the formulation has improved resistance to some common drug-abuse tampering methods. The geopolymer matrix has the potential to make the opioid product less accessible and attractive to non-medical users.

Geopolymers have been suggested to use as construction, waste treatment and fire proof materials and even drug delivery material due to its excellent mechanical strength, chemical stability and flame resistance. The aim of this study was to investigate the influence of temperature, time and humidity during curing on mechanical strength and porosity of geopolymers.

The geopolymer precursor paste was obtained by mixing metakaolin, waterglass and de-ionized water. The paste was molded into cylindrical rubber moulds (6 12 mm) and cured under different conditions: i.e. temperatures (ambient temperature, 37°C and 90°C), humidity and time (24, 48 and 96 hours). The compressive strength was determined using a universal testing machine. Helium pycnometer was used to measure the porosity. Via x-ray diffraction the phase composition of the cured samples was determined.

Elongated curing slightly decreased the total porosity of the tested geopolymers. Higher curing temperature increased the compressive strength after 24 hour but did not affect strength for longer curing times. In general, the samples cured in moisture had higher mechanical strength than those cured in air. But low compression strength of samples cured under high temperature and long time showed that some water content in geopolymer was essential to retaining its microstructure.

To reduce the effort required to penetrate the skin and optimize drug release profiles, bioceramic microneedle arrays with higher-aspect-ratio needles and a flexible and self-swelling substrate have been developed. Swelling of the substrate can assist in separating it from the needles and leave them in the skin as a drug depot. The preparation procedures for this bioceramic microneedle are described in the paper. Clonidine hydrochloride, the model drug, was released in a controlled manner by the microneedle device in vitro. Results showed that the microneedle array with a flexible and self-swelling substrate released the drug content faster than the array with a rigid substrate. Disintegration of the needle material and diffusion of the drug molecules are believed as the main control mechanisms of the drug release from these microneedle arrays. Ex vivo skin penetration showed that they can effectively penetrate the stratum corneum without an extra device. This work represents a progression in the improvement of bioceramic microneedles for transdermal drug delivery.

Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered axonal re-growth, something current CI technology cannot provide.

The results show that human and murine inner-ear ganglion neurites and, potentially, neural progenitor cells can attach to patterned NCD surfaces without an extracellular matrix coating. Microscopic methods revealed adhesion and neural growth, specifically along the nail-head-shaped NCD pillars in an ordered manner, rather than in non-textured areas. This pattern was established when the inter-NCD pillar distance varied between 4 and 9 lm.

The findings demonstrate that regenerating auditory neurons show a strong affinity to the NCD pillars, and the technique could be used for neural guidance and the creation of new neural networks. Together with the NCD’s unique anti-bacterial and electrical properties, patterned NCD surfaces could provide designed neural/electrode interfaces to create independent electrical stimulation signals in CI electrode arrays for the neural population.

Fabrication of multifunctional ultrasound contrast agents (UCAs) has been recently addressed by several research groups. A versatile strategy for the synthesis of UCA precursors in the form of biodegradable vesicles with a biocompatible crosslinked polymer shell is described. Upon ultrasound irradiation, acoustic droplet vaporization transforms such particles into microbubbles behaving as UCAs. This proof of concept entails the features of a potential theranostic microdevice.

Fabrication of multifunctional ultrasound contrast agents (UCAs) has been addressed by many research groups.1,2 Recently a poly(vinyl alcohol) shelled microbubble 3 has shown a remarkable chemical and physical stability and versatility for the surface functionalization, leading to a platform for multimodality imaging (ultrasounds, magnetic resonance, single photon emission computer tomography) and targeting inflammation and tumours4. In this contribution we present a new strategy for the synthesis of UCAs precursors in the form of vesicles with a biodegradable crosslinked polymer shell.

Methods

Deposition of methacryloyl-derivative of hydrophilic and biodegradable polymers as dextran (DexMA50) or hyaluronic acid (HAMA30) on a lipid vesicle with a liquid perfluoropentane core, 5,6 followed by a photopolymerization of the methacrylate moiety allows the obtainment of polymer shelled vesicles.

Results

Lipid shelled vesicles with a perfluorocarbon (PFC) core (Figure 1a) undergo an acoustic droplet vaporization (ADV),7 upon ultrasounds (US) irradiation, transforming such particles into ultrasound effective microbubbles (Fig 1b). The process is reversible as the US are switched off (Fig 1c). In the “microbubble” state, i.e. during US irradiation, the system is echogenic at low mechanical index, allowing their use as UCAs. In this contribution we show that additional functions can be implemented into the microbubbles. For example, we demonstrated the possibility to obtain shells with a thermoreversible behaviour.

Conclusions

This new class of polymer shelled vesicles/microbubbles entails features desired in a potential theranostic microdevice.

The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.

The high stiffness of acrylic bone cements has been hypothesized to contribute to the increased number of fractures encountered after vertebroplasty, which has led to the development of low-modulus cements. However, there is no data available on the in vivo biocompatibility of any low-modulus cement. In this study, the in vitro cytotoxicity and in vivo biocompatibility of two types of low-modulus acrylic cements, one modified with castor oil and one with linoleic acid, were evaluated using human osteoblast-like cells and a rodent model, respectively. While the in vitro cytotoxicity appeared somewhat affected by the castor oil and linoleic acid additions, no difference could be found in the in vivo response to these cements in comparison to the base, commercially available cement, in terms of histology and flow cytometry analysis of the presence of immune cells. Furthermore, the in vivo radiopacity of the cements appeared unaltered. While these results are promising, the mechanical behavior of these cements in vivo remains to be investigated.

Lindhe Xtend is a prosthetics company in Halmstad with the ambition of providing the amputee with functional mobility and a high quality of life. Their main product, the Xtend Foot is a patented prosthetic foot developed to imitate the natural features of the human foot.

Dissatisfaction with prostheses often stems from poor fitting of the part that connects to the body. This often leads to chafing, pistoning and strain. Amongst users of leg prostheses, the strain often results in a reduction of limb volume, further augmenting the bad fit. The development of suspension systems has excelled through the recent years as many prosthetics companies has developed products with integrated vacuum assisted suspension systems, a mounting method where vacuum is used to hold the prosthesis against the body. This mounting mechanism of the limb onto the prosthesis has been proven to prevent fluctuations of limb volume as well as reducing chafing and pistoning.

A vacuum assisted suspension system integrated with the Xtend Foot has been invented using the product development process. The project group has used motion analysis, calculations and concept generation to reach a final concept to be prototyped, called Unify Xtend. Unify Xtend is made to demonstrate the function of the final concept, to actively produce a vacuum during ambulation using a pneumatic actuator.

This project has addressed prosthetics and pneumatics. The project group has, using their knowledge of mechanical engineering and physiology, combined and applied them in this thesis.

Further user testing is needed to evaluate the usability of the prototype, due to reaching target pressure considerably faster than the products of main market competitors.

Human grasping and manipulation control critically depends on tactile feedback. Without this feedback, the ability for fine control of a prosthesis is limited in upper limb amputees. Although various approaches have been investigated in the past, at present there is no commercially available device able to restore tactile feedback in upper limb amputees. Based on the Discrete Event-driven Sensory feedback Control (DESC) policy we present a device able to deliver short-lasting vibrotactile feedback to transradial amputees using commercially available myoelectric hands. The device (DESC-glove) comprises sensorized thimbles to be placed on the prosthesis digits, a battery-powered electronic board, and vibrating units embedded in an arm-cuff being transiently activated when the prosthesis makes and breaks contact with objects. The consequences of using the DESC-glove were evaluated in a longitudinal study. Five transradial amputees were equipped with the device for onemonth at home. Through a simple test proposed here for the first time-the virtual eggs test-we demonstrate the effectiveness of the device for prosthetic control in daily life conditions. In the future the device could be easily exploited as an add-on to complement myoelectric prostheses or even embedded in prosthetic sockets to enhance their control by upper limb amputees.

Purpose - The purpose of this paper is to study the use of the additive manufacturing (AM) method, electron beam melting (EBM), for manufacturing of customized hip stems. The aim is to investigate EBM's feasibility and commercial potential in comparison with conventional machining, and to map out advantages and drawbacks of using EBM in this application. One part of the study concerns the influence on the fatigue properties of the material, when using the raw surface directly from the EBM machine, in parts of the implant.Design/methodology/approach - The research is based on a case study of manufacturing a batch of seven individually adapted hip stems. The stems were manufactured both with conventional machining and with EBM technology and the methods were compared according to the costs of materials, time for file preparation and manufacturing. In order to enhance bone ingrowths in the medial part of the stem, the raw surface from EBM manufacturing is used in that area and initial fatigue studies were performed, to get indications on how this surface influences the fatigue properties.Findings - The cost reduction due to using EBM in this study was 35 per cent. Fatigue tests comparing milled test bars with raw surfaced bars indicate a reduction of the fatigue limit by using the coarse surface.Originality/value - The paper presents a detailed comparison of EBM and conventional machining, not seen in earlier research. The fatigue tests of raw EBM-surfaces are interesting since the raw surface has shown to enhance bone ingrowths and therefore is suitable to use in some medical applications.

BACKGROUND: Glenohumeral displacements assessment would help to design shoulder prostheses with physiological arthrokinematics and to establish more biofidelic musculoskeletal models. Though displacements were documented during static tasks, there is little information on their 3D coupling with glenohumeral angle during dynamic tasks. Our objective was to characterize the 3D glenohumeral displacement-rotation couplings during dynamic arm elevations and rotations.

METHODS: Glenohumeral displacements were measured from trajectories of reflective markers fitted on intracortical pins inserted into the scapula and humerus. Bone geometry was recorded using CT-scan. Only four participants were recruited to the experiment due to its invasiveness. Participants performed dynamic arm abduction, flexion and axial rotations. Linear regressions were performed between glenohumeral displacements and rotations. The pin of the scapula of one participant moved, his data were removed from analysis, and results are based on three participants.

FINDINGS: The measurement error of glenohumeral kinematics was less than 0.15mm and 0.2°. Maximum glenohumeral displacements were measured along the longitudinal direction and reached up to +12.4mm for one participant. Significant couplings were reported especially between longitudinal displacement and rotation in abduction (adjusted R(2) up to 0.94).

INTERPRETATION: The proposed method provides the potential to investigate glenohumeral kinematics during all kinds of movements. A linear increase of upward displacement during dynamic arm elevation was measured, which contrasts with results based on a series of static poses. The systematic investigation of glenohumeral displacements under dynamic condition may help to provide relevant recommendation for the design of shoulder prosthetic components and musculoskeletal models.

Zirconia/alumina ceramics possess outstanding mechanical properties for dental and orthopedic applications, but due to their poor surface bioactivities they exhibit a weak bone-bonding ability. This work proposes an effective 30-min solution treatment which could successfully induce formation of bone-like apatite on the surface of 3Y-TZP and a ternary composite composed of yttria-stabilized zirconia, ceria-stabilized zirconia, and alumina (35 vol% 3Y-TZP + 35 vol% 12Ce-TZP + 30 vol% Al2O3) after 3 weeks immersion in simulated body fluid (SBF). XRD was used for phase identification in the ceramic materials. The influence of solution treatment on the surface chemistry and its role on apatite formation were investigated via SEM, EDS and XPS. In vitro apatite-forming ability for the solution-treated and untreated samples of the composite and individual substrates of 3Y-TZP, 12Ce-TZP, and Al2O3 was evaluated by immersion in SBF. Apatite crystals were formed only on 3Y-TZP and composite substrates, implying that it is mainly the 3Y-TZP constituent that contributes to the bioactivity of the composite. Further, it was found from the XPS analysis that the zirconia material with higher phase stability (12Ce-TZP) produced less ZrâOH functional groups on its surface after solution treatment which accounts for its weaker bioactivity compared to 3Y-TZP.